Project Summary Significance and Rationale: Deregulation of normal tissue repair processes has dramatic consequences for life quality and survival of patients. Together, insufficient healing (chronic wounds) and excessive repair after injury (scarring/fibrosis) cause healthcare costs that reach tens of billions of dollars per year in the US; these costs are expected to further increase with our aging populations. Chronic and fibrotic healing occur when the bodys own repair capacity is either impaired or overwhelmed. One approach in regenerative medicine is to replace injured, diseased or aged tissues with functional tissue equivalents. This approach often fails because of adverse host reactions that are part of the repair program, e.g., immune, inflammatory, and fibrotic responses. Thus, regenerative medicine increasingly considers to support the adults bodys own regenerative capacities to promote closure of wounds that never heal and to keep excessive repair at bay. However, it is still unclear why humans lost regenerative capacity during evolution, whereas lower organisms can regenerate whole organs. Understanding the underlying common control mechanisms will help to devise novel strategies to regenerate rather than repair organ injuries to extend the healthy life expectancy of our aging population. Objective: There is a fundamental need for innovative, transformational, and interdisciplinary research to understand how ?dormant? regeneration processes can be activated and exploited in a controlled manner to promote human adult organ regeneration. It is the overarching objective of the Gordon Research Conference on Tissue Repair and Regeneration (GRC-TRR) to foster interdisciplinary discussions and collaborations that will deliver the next generation of discoveries in regenerative medicine. Aims and Approach: Aim 1: To establish the GRC-TRR as the premier and unique forum to discuss regene- rative medicine among experts from different disciplines that would otherwise not meet. Great diversity has always been and will be the greatest strength of the GRC-TRR. We will bring together fundamental and translational scientists studying different aspects of repair/regeneration using a wide variety of experimental models and approaches. Aim 2: To support junior investigators so that they can present their work to peers and leaders in the field, learn about, and become integrated into this research community. As for the past three meetings, the GRC-TRR will host a preceding Gordon Research Seminar (GRS), organized for and by graduate students and postdocs who will stay for the GRC. Aim 3: To defray the travel and registration costs of GRS and GRC-TRR speakers to stimulate their attendance over the whole meeting. From the great success of the intimate and no-intimidating setting of previous GRC-TRRs, we can expect relationships to be forged at this meeting that will last for decades to come. We will also encourage participation by underrepresented minorities, through scholarships offered by existing GRC programs. Generous NIH support will greatly enhance the quality of the program and the ultimate success of the GRS/GRC-TRR.